Problem Statement Research Objectives Benefits of Research Review of References

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B. Problem Statement

Based on the above, description the formulation of the problem defined as follows: Did the administration of P. niruri L extract affect the immunologic status and development of colon cancer in 1.2 DMH-induced Sprague-Dawley rats?

C. Research Objectives

This study was conducted to analyze the effects of P. niruri L extract on the infiltration of lymphocytes, expression of perforin, apoptotic index, cancer cell proliferation and tumor growth of colon in 1.2 DMH-induced Sprague-Dawley rats.

D. Benefits of Research

The benefit of this research results from the science perspective is a scientific explanation about the effects of P. niruri L against the development of colon cancer. The results of this study is expected to add the repertoire of knowledge in the field of oncology, pathology anatomy, immunology and the scientific foundation of the use of medicinal plants, especially P. niruri L. The benefit to health services is to provide input and insight for public health care institutions about the potency of P. niruri L scientifically as the basis for the development of adjuvant chemoimmunotherapy against colon cancer. For the community of user, the results of this study is expected to be scientific information about the benefit of P. niruri L in treatment of colon malignant as an herbal complementary medicine to chemotherapy. The result of this research is expected to be reference for the next research to treatment of colon cancer.

E. Review of References

The ability of the immune system to protect the body from disease is a new approach in cancer therapy known as immunotherapy is aimed to modulate xxvi support the immune system so that it is better able to combat cancer cells. In addition locoregionally therapy, also simultaneously generate a systemic immune system. Efficacy P. niruri L in modulating the immune system has been proved in both animals experimental and in humans. Immunological tests in mice show that extract of P. niruri L act as immunostimulator. There was no reports regarding symptoms of toxicity or side effects of P. niruri L in both animals and in humans experimental, for short and long-term use. The function of immune system in relation to immunity against the tumor is called the protective function of immune surveillance through recognizing and then eliminating the abnormal cells before tumor was formed or combat the tumor cells. This concept should theoretically ensures apoptosis of cancer cells. Immunocompetence cells that plays an important role in immunity against tumors are Cytotoxic T lymphocyte CTL, Natural Killer cells NK, macrophages and B lymphocytes. NK cells and CTL express their anti-tumor activity through secretion of perforin and cytoplasm molecules that break down granzym controlling apoptosis and cytokine production. Intraepithelial lymphocyte infiltration is strongly associated with improved prognosis of colorectal cancer patients. Understanding the behavior of cancer is very important in determining therapy and it’s prognosis prediction. Therefore, better understanding of cancer processes, cell cycle abnormalities and measurement of biomolecullar markers such as cell proliferation and apoptotic activity associated with therapeutic response and patient survival are needed. Inbalance between proliferation and apoptosis become the basis of neoplasm progression. Measurement of cell proliferation activity was based on abnormalities in the cell cycle, one of them can be done by the method of reaction of Ag with NORs. Protein AgNORs argyrophilic nucloelar organizer regions is a protein that accumulates in the cell during hyper-proliferation, in contrast to cells that do not proliferate, they are very little expression. AgNORs examination , is deemed appropriate methode to describe the activity of ribosomal DNA transcription, are strongly associated with cell cycle and proliferation of malignant cells. xxvii Apoptosis plays an important role in the regulation of the immune system and elimination of cells undergoing DNA damage is irreparable. Dysregulating of apoptosis resulted in cells with DNA damage survive, which in turn increases the risk of mutation. Detection of apoptotic bodies that are expressed by cancer cells, among others, can be done by the method of Terminal deoxynucleotidyl transferase-mediated dUTP Nick End Labeling TUNEL in colon cancer histological tissue sections.

F. Methods